L0301P52 - Effects of Cancer
Cancer *neoplasia - clinical term for cancer *second to heart disease as the highest cause of death *causes much human suffering *results from damage to DNA **can be acquired or inherited *is not a single disease **outcome and prognosis of the cancer depends on the cell type of origin and the tissue of origin **type of cancer cell will have a large impact on treatment modalities ***surgery, chemotherapy or no treatment **progression of the cancer depends on the cell type in which the cancer arose **some types are more slow growing and less likely to spread *can take years for the tumour to develop Chemotherapy *kills cancer cells but also many healthy cells Statistics Most commonly diagnosed: #prostate #bowel #breast Most common causes of death: #lung #*silent cancer - doesn’t present symptoms until it has reached a late stage where treatment is not effective #bowel #prostate #breast Cancer Types Different types of cancer occur as there are different cell types in tissues and organs *carcinomas **make up 85% of all cancers **arise from skin and epithelial cells that line organs ***breast, lung, colon cancer *sarcomas **arise from bone, muscle, blood vessels *lymphoma **arise from lymphoid cells *leukemias **arise from white cells of the bone marrow Cell Characteristics *reproduce despite normal constraints that inhibit cell proliferation and clonal expansion **normally a cell only divides following growth factor or hormone stimulation **however cancer cells loses control over cell cycle and division *has the ability to invade and colonise territories normally reserve for other cells **secondary tumours - generally cause death of the patient Unregulated Cell Growth *autonomous/deregulated cell growth is the defining feature of all cancers (neoplasms) *deregulated cell growth is a combination of increased cell proliferation and decreases apoptosis - balance has been disrupted Molecular Medicine *caused by the accumulation of genetic alterations that confer a survival advantage to the cancer cell *mutations cause changes that may result in: **increased cell growth **resistance to apoptosis **altered tissue invasiveness **angiogenic proliferation (formation of blood vessels to support the cancer cells) **ability to escape immune surveillance *genetic nature of cancer **reflected in clonal nature of cancer cells **i.e. daughter cells inherit the properties of the mother cell *recognition that cancer is genetic has lead to intensive effort to characterise genes responsible which has lead to new therapies Characteristics *cell transformation - change from a normal cell to a cancer cell *pathologist uses the change in appearance of the cell to diagnose the cancer *looks very different to normal cells: **enlarged nucleus (cell size increases) **cytoskeleton changes **loss of specialised features *spectrum of changes in appearance **longer progression = more change **highly malignant cancers = not possible to tell the cell of origin *as cancer develops, genetic errors and changes in cell appearance increases Tumours Benign Tumours *do not cause too much trouble unless grown in a confined space (brain) *remain localised and do not spread **exceptions do exist: some become malignant after a certain period of time = pre-malignant, e.g. cells of colon, cervix *appear like the tissues they came from (under the microscope) Malignant Tumours *microscopically do not result the tissue or cell of origin *often have irregular structures - large variable nucleus, little cytoplasm, evidence of mitosis, little specialised structures *can spread and invade surrounding tissues Difference between Cancer vs Normal Cells *malignant cells are all members of a single clone, including those that have spread *different than surrounding normal cells **divide at a faster rate **have a higher metabolic rate **invade new tissues Metastasis *cancer cells invading other tissues and spreading to other parts to the body *can be local or distant *moves locally or through the blood stream or lymphatic system *spread of cancer may depend on the type **i.e. some cancers are more likely to spread than others **e.g. small cell lung cancer has often spread by the time symptoms present Molecular Mechanisms *for cancer cells to metastasise it requires genetic change that lead to change in the cells function and appearance: **decreased adherence to neighbouring cells = increased ability to move **extend into surrounding tissue by degrading ECM i.e. secrete proteolytic enzymes to migrate into lymphatics and blood vessels **need to be able to provide its own adequate blood supply ***angiogenesis: development of a new microcirculation by secretion of vascular endothelial growth factor Growth Advantage *cancer cells that acquire these characteristics have a growth advantage, will be clonally selected, and will grow and proliferate given a suitable environment **i.e. the original cancer cell had a growth advantage giving rise to the rest *cancer cell acquires growth advantages via mutations to DNA *daughter cells inherit the genetic mutations and therefore inherit the growth advantage *cancer cells from an individual cancer tend to look the same - all related as daughter cells inherit the same abnormalities   Effects of Cancer Local Effects *displaces normal adjacent tissue *function of the tissue deteriorates as the normal cells are replaced by cancer cells which are immature and cannot perform normal specialised function **may lead to organ failure **e.g. bone marrow - makes blood cells but cannot do that when leukemias occur **e.g. brain - replace and crowds out the brain tissue *can block vital passages **arteries, veins, lymph nodes - leads to significant symptoms *mass of a tumour may become very large and block the lumen of organs *have very rapid growth and turnover = high metabolic rate which competes with normal cells for nutrition and blood supply **some organs may break down their own proteins to nourish the cancer = severe weight loss of the patient *cachexia - profoundly wasted **weight loss, fatigue and tiredness (seen in stage 4 cancer patients) Distant Effects *metastasis = common cause of cancer related deaths *spreading occurs via: **lymphatics: lymph nodes, lymphatics and then into venous circulation, lungs, heart and via circulation to other organs **blood stream: circulation - distal organs *may secrete hormones which cause distant effects - non-metastatic manifestations **lung cancer secretes cortisol Regulation of Metastatic Deposition *site of primary tumour *venous drainage from primary site *actual size of cancer cells *e.g. **both the lung and the liver are frequent serious sites for the spread of cancer **may relate to the size of the cancer cells versus the size of the capillaries in these organs – the cancer cells get stuck and then adhere and grow in that site Bone Metastases *most frequent in patients with breast and or prostate cancer although it may not relate to having an aggressive tumour *leads to hypercalcaemia, osteolytic lesions (holes in bone), fractures, osteoporosis, *wearing of bone may lead to deformities: nerve and spinal cord compression due to vertebral body collapse *extravasation **formation of secondary tumours when cancer cells are forced out from the vessel into surrounding tissue Cancer Dormancy *cancers may reappear decades after excision of the primary tumour *seen with breast and melanoma cancer *may result from one cancer cell not being removed and it spreading **failure of the cancer micrometastasis to develop its own blood vessels – therefore the tumour may survive but not expand **begins to expand and grow when it acquires an increased blood supply (angiogenic switch) *new therapeutic strategies in anti-angiogenic therapies may stop tumour proliferation